Grapefruit juice intake does not enhance but rather protects against aflatoxin B

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http://carcin.oupjournals.org/cgi/content/abstract/25/2/203

Carcinogenesis Advance Access originally published online on October

24, 2003

Carcinogenesis, Vol. 25, No. 2, 203-209, February 2004

© Oxford University Press; all rights reserved

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MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

Grapefruit juice intake does not enhance but rather protects against

aflatoxin B1-induced liver DNA damage through a reduction in hepatic

CYP3A activity

Masaaki Miyata1, Hiroki Takano, Lian Q. Guo, Kiyoshi Nagata and

Yasushi Yamazoe

Division of Drug Metabolism and Molecular Toxicology, Graduate

School of Pharmaceutical Sciences, Tohoku University, Aramaki, Aoba-

ku, Sendai 980-8578, Japan

Influence of grapefruit juice intake on aflatoxin B1 (AFB1)-induced

liver DNA damage was examined using a Comet assay in F344 rats given

5 mg/kg AFB1 by gavage. Rats allowed free access to grapefruit juice

for 5 days prior to AFB1 administration resulted in clearly reduced

DNA damage in liver, to 65% of the level in rats that did not

receive grapefruit juice. Furthermore, rats treated with grapefruit

juice extract (100 mg/kg per os) for 5 days prior to AFB1 treatment

also reduced the DNA damage to 74% of the level in rats that did not

receive grapefruit juice. No significant differences in the portal

blood and liver concentrations of AFB1 were observed between

grapefruit juice intake rats and the controls. In an Ames assay with

AFB1 using Salmonella typhimurium TA98, lower numbers of revertant

colonies were detected with hepatic microsomes prepared from rats

administered grapefruit juice, compared with those from control

rats. Microsomal testosterone 6ß-hydroxylation was also lower with

rats given grapefruit juice than with control rats. Immunoblot

analyses showed a significant decrease in hepatic CYP3A content, but

not CYP1A and CYP2C content, in microsomes of grapefruit juice-

treated rats than in non-treated rats. No significant difference in

hepatic glutathione S-transferase (GST) activity and glutathione

content was observed in the two groups. GSTA5 protein was not

detected in hepatic cytosol of the two groups. In microsomal

systems, grapefruit juice extract inhibited AFB1-induced mutagenesis

in the presence of a microsomal activation system from livers of

humans as well as rats. These results suggest that grapefruit juice

intake suppresses AFB1-induced liver DNA damage through inactivation

of the metabolic activation potency for AFB1 in rat liver.

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